Deriving toxicological reference values for dietary inorganic arsenic exposure from epidemiological evidence of cardiovascular disease risk.

The toxicity of arsenic has been well established for millennia, with epidemiological data demonstrating the association of inorganic arsenic (iAs) to cancers and dermal defects. Recently, epidemiological and mechanistic studies linking dietary iAs exposure to cardiovascular diseases (CVD) have emerged. Despite growing evidence on iAs induced CVD, current toxicological reference values (TRVs) for dietary iAs are largely based on cancer, peripheral vascular ("blackfoot") disease, diabetes and dermal endpoints. To bridge this gap, the current study estimated TRVs for food borne iAs using the benchmark dose (BMD) approach, by modeling dose-response data of multiple CVD endpoints identified from literature. The estimated TRVs for CVD incidence were in the range of 0.027-0.037 μg/kg bw/day and were lower than TRVs estimated by regulatory bodies. TRVs estimated based on CVD mortality alone were in the range of 0.074-0.729 μg/kg bw/day. A TRV of 0.03 μg/kg bw/day based on coronary heart disease incidence was considered appropriate from a regulatory standpoint. The TRV estimate suggests that iAs induced cardiovascular diseases are an important endpoint from a policymaking perspective on maximum allowable arsenic levels in food.